vided) Telomerase is an RNA-dependent reverse transcriptase involved in the maintenance of eukaryotic chromosomal ends through the production of telomeres. Many of the components involved in the formation of the telomerase ribonucleoprotein (RNP) complex have yet to be determined or characterized, although telomerase activity and telomere length have been implicated in both aging and cancer. Recently, the secondary structure of the essential RNA component of human telomerase (hTR) was proposed based on the phylogenetic analysis of the telomerase RNA gene from 32 vertebrate species. The pseudoknot domain is contained within the minimal region of hTR that is absolutely required for catalytic activity. The specific aims of this proposal are to use multidimensional, multinuclear NMR techniques to investigate the structure of the conserved pseudoknot domain and to investigate the interactions between this domain and two proteins, ribosomal protein L22 and hStau, which have been shown to interact with the hTR pseudoknot domain. The effects of protein binding on the structure of the pseudoknot domain will be investigated as a precursor to solving the solution structure of the protein-RNA complex.